GAS8

growth arrest specific 8, the group of Dynein regulatory complex

Basic information

Region (hg38): 16:90019628-90044975

Previous symbols: [ "GAS11" ]

Links

ENSG00000141013 ∙ NCBI:2622 ∙ OMIM:605178 ∙ HGNC:4166 ∙ Uniprot:O95995 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 33 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 33 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia 33 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 33	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	26387594

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GAS8 gene.

• Primary ciliary dyskinesia 33 (224 variants)
• not provided (73 variants)
• Inborn genetic diseases (24 variants)
• not specified (5 variants)
• Primary ciliary dyskinesia (1 variants)
• GAS8-related condition (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAS8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	46	9	57
missense			116	13	5	134
nonsense	3					3
start loss			1			1
frameshift	2	1				3
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2	1			3
splice region			4	7		11
non coding			2	31	44	77
Total	5	3	124	90	58

Highest pathogenic variant AF is 0.0000197

Variants in GAS8

This is a list of pathogenic ClinVar variants found in the GAS8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-90022379-G-A			Benign (Nov 11, 2018)
16-90022496-C-G			Benign (Nov 11, 2018)
16-90022715-T-G		Primary ciliary dyskinesia 33	Benign (Nov 22, 2023)
16-90022722-A-G		Primary ciliary dyskinesia 33	Uncertain significance (Oct 22, 2021)
16-90022722-A-T		Primary ciliary dyskinesia 33	Uncertain significance (Dec 16, 2021)
16-90022728-AGCAGGG-A		Primary ciliary dyskinesia 33	Likely benign (Sep 14, 2023)
16-90022730-C-T		Primary ciliary dyskinesia 33	Uncertain significance (Oct 13, 2022)
16-90022735-G-C		Primary ciliary dyskinesia 33	Likely benign (Jan 18, 2022)
16-90022737-G-A		Primary ciliary dyskinesia 33	Benign (Jan 22, 2024)
16-90022899-C-T			Benign (May 24, 2019)
16-90022905-C-T			Benign (Dec 31, 2018)
16-90022927-C-T			Benign (Nov 11, 2018)
16-90022960-C-T			Likely benign (Sep 24, 2021)
16-90023055-C-G			Benign (Dec 31, 2018)
16-90027561-T-C			Benign (Nov 11, 2018)
16-90027616-C-T		Primary ciliary dyskinesia 33	Likely benign (Nov 01, 2022)
16-90027618-C-G		Primary ciliary dyskinesia 33	Likely benign (Aug 18, 2023)
16-90027620-A-G		Primary ciliary dyskinesia 33	Likely benign (Jul 07, 2023)
16-90027629-A-C		Primary ciliary dyskinesia 33	Likely benign (Dec 25, 2023)
16-90027641-G-A			Likely benign (Mar 29, 2018)
16-90027649-A-G		Primary ciliary dyskinesia 33	Uncertain significance (Jan 11, 2022)
16-90027663-A-G		Primary ciliary dyskinesia 33	Uncertain significance (Aug 15, 2022)
16-90027670-A-G		Primary ciliary dyskinesia 33	Benign (Jan 29, 2024)
16-90027674-C-T		Primary ciliary dyskinesia 33	Likely benign (Aug 15, 2022)
16-90027677-C-A		Primary ciliary dyskinesia 33 • GAS8-related disorder	Benign (Jan 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAS8	protein_coding	protein_coding	ENST00000268699	11	25347

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.09e-12	0.157	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.919	339	295	1.15	0.0000193	3137
Missense in Polyphen		83	75.57	1.0983		767
Synonymous	-0.539	128	120	1.06	0.00000787	873
Loss of Function	0.817	21	25.4	0.825	0.00000133	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000898	0.000897
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000163	0.000158
Middle Eastern	0.000326	0.000272
South Asian	0.0000999	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the nexin-dynein regulatory complex (N- DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays an important role in the assembly of the N-DRC linker (By similarity). Plays dual roles at both the primary (or non-motile) cilia to regulate hedgehog signaling and in motile cilia to coordinate cilia movement. Required for proper motile cilia functioning (PubMed:26387594, PubMed:27120127, PubMed:27472056). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by faciltating the trafficking of SMO into the cilium and the stimulation of SMO activity in a GRK2-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q60779, ECO:0000250|UniProtKB:Q7XJ96, ECO:0000269|PubMed:26387594, ECO:0000269|PubMed:27120127, ECO:0000269|PubMed:27472056}.

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.778
• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.5

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.282
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.919

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gas8
• Phenotype: growth/size/body region phenotype; cellular phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: gas8
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: epithelial cilium movement;determination of left/right symmetry;brain development;negative regulation of cell population proliferation;flagellated sperm motility;cellular protein localization;axoneme assembly;positive regulation of smoothened signaling pathway;cilium movement involved in cell motility;positive regulation of protein localization to cilium;regulation of microtubule binding
• Cellular component: Golgi apparatus;microtubule;cilium;axoneme;motile cilium;ciliary basal body;sperm flagellum
• Molecular function: molecular_function;protein binding;microtubule binding;Rab GTPase binding